Isolation and Characterization of Natural and Recombinant Cyclophilins

Abstract

Cyclophilins (Cyp’s) are members of a class of proteins which bind the pharmaceutically important immunosuppressive agent cyclosporin A (CsA) and its analogs (1–5). In addition to selectively binding CsA, these proteins have proven to be enzymes which accelerate the cis-trans isomerization of proline containing peptide bonds in vitro (8, 9) and the rate of protein folding in vitro (8–13). Recently. another member of the peptidyl-prolyl isomerase family (PPIases) has been identified, the FK binding proteins (FKBP’s) (52, 53). The FKBP’s have very little sequence homology with the Cyp’s and were initially identified as the binding proteins for the potent immunosuppressant FK-506 and its analogs (52–54). Although Cyp and FKBP are both PPIases, they apparently do not have the same specificity for peptide substrates (16) and Cyp will not bind FK-506 nor will FKBP bind CsA (52, 53).